In the coming year our design to better define the pathogenesis and pathologic consequences of the neurofibrillary pathology in a specific model system, Beta, Beta-iminodipropionitrile (IDPN) exposure. Rats intoxicated with this agent develop proximal axonal swellings filled with neurofilaments. Previous studies have shown that slow axonal transport of neurofilament proteins is impaired. This change occurs early after administration, and current evidence suggests that the impaired nurofilament transport may underlie subsequent structural changes in the axon, including the proximal axonal swelling and late atrophy of axons distal to the swellings. Ongoing studies are directed toward further elucidation of the mechanism of transport abnormality, further pathologic definition of the model, and correlation of the changes with those seen in motor neuron diseases.